@article{18851, keywords = {Adjuvants, Immunologic, Bacterial Proteins, CD4-Positive T-Lymphocytes, Chaperonin 60, Chaperonins, Cytokines, HLA-DR Antigens, Heat-Shock Proteins, Humans, leprosy, Mycobacterium leprae, Mycobacterium tuberculosis, Polymorphism, Genetic, Th1 Cells, Th2 Cells}, author = {Mitra D K and Rajalingam R and Taneja V and Bhattacharyya B C and Mehra N K}, title = {HLA-DR polymorphism modulates the cytokine profile of Mycobacterium leprae HSP-reactive CD4+ T cells.}, abstract = {
In the present study, in vitro attempts have been made to define the cytokine profile of CD4+ T cells from polar leprosy patients and healthy individuals against Mycobacterium leprae-derived heat shock proteins (HSPs), HSP65 and HSP18, and their trypsin-digested fragments, relating to HLA-DR polymorphism. While all tryptic fragments of optimal digestion and undigested HSPs could stimulate CD4+ T cells from tuberculoid (TT) leprosy patients and healthy contacts (stimulation index, SI > 2.0), only two fragments, TDB65-2 (18 kDa) and TDB18-3 (3 kDa) triggered CD4+ T cells of anergic lepromatous (LL) leprosy patients. Both of these HSPs and their tryptic fragments showed diverse HLA-DR restriction, with DR15 providing the strongest restriction. Cytokine analysis demonstrated that HSP65 and HSP18 induced Th1-like activity in the context of all the restricting HLA-DR alleles, except DR1 and DR7 which induced a Th2 type of response against HSP65 and HSP18, respectively. These Th2 inducer epitopes on HSP65 (DR1 restricted) and HSP18 (DR7 restricted) were absent from TDB65-2 and TDB18-3 which exclusively triggered Th1 cells in both TT and LL forms of leprosy in the context of multiple DR alleles, DR15 being the major antigen-presenting allele. These studies suggest that the major histocompatibility complex phenotype of the antigen-presenting cell can modulate Th1-like versus Th2-like activity against M. leprae pathogens in leprosy and healthy individuals.
}, year = {1997}, journal = {Clinical immunology and immunopathology}, volume = {82}, pages = {60-7}, month = {1997 Jan}, issn = {0090-1229}, doi = {10.1006/clin.1996.4282}, language = {eng}, }